Etiology

Mainly children < 5 years of age

• Bacterial exotoxins

  • Shiga-like toxin (verotoxin)

    • From enterohemorrhagic E. coli (EHEC) strain O157:H7

    • Usually transmitted via contaminated foods (e.g., undercooked beef or raw leafy vegetables)

  • Shiga toxin produced by Shigella dysenteriae

• Streptococcus pneumoniae infection

• Atypical hemolytic uremic syndrome: Complement dysregulation (hereditary or acquired) accounts for approx. 5% of HUS cases with noninfectious etiologies, referred to as atypical HUS (aHUS)

HUS is a thrombotic microangiopathy, a condition characterized by the formation of microthrombi occluding the microvasculature. The other main thrombotic microangiopathy is thrombotic thrombocytopenic purpura (TTP). The two conditions have some pathophysiology and clinical findings in common, but different etiologies. HUS is caused by bacterial toxins. [4]

1. Infection with enterohemorrhagic E. coli (EHEC) or another causative organism

2. Mucosal inflammation facilitates bacterial toxins entering systemic circulation.

3. Toxins cause endothelial cell damage (especially in the glomerulus ).

4. Damaged endothelial cells secrete cytokines that promote vasoconstriction and platelet microthrombus formation at the site of damage (intravascular coagulopathy) → thrombocytopenia (consumption of platelets)

5. RBCs are mechanically destroyed as they pass through the platelet microthrombi occluding small blood vessels (i.e., arterioles, capillaries) → hemolysis (schistocytes), and end-organ ischemia and damage, especially in the kidneys → decreased glomerular filtration rate (GFR)

E. coli O157:H7 infection → Shiga-like toxin in systemic circulation → toxin-mediated endothelial injury → microthrombus formation → blockage of small vessels → RBC fragmentation (hemolysis) and end-organ damage